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STIMIILATM  OF  AFFEEEMBfES. 


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PRESENTED    TO  THE  BOARD  OF  UNIVERSITY  STUDIES  OF 

THE  JOHNS  HOPKINS  UNIVERSITY  FOR  THE  DEGREE 

OF  DOCTOR  OF  PHILOSOPHY, 


BY 
REID   HUNT,   A.B. 


REPRINTED  FROM 

THE  JOURNAL  OF  PHYSIOLOGY,  VOL.  XVIII 

1895. 


Columbia  ©nitJf  rsiftp 

tntlieCitpoflifttjgork 

CoUege  of  ^ijpsiicianfi  anb  burgeons 
Hibvarp 


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THE  FALL  OF  BLOOD-PEESSURE  EESETIf  FEOM 
TBE  STIMULATION  OF  AFFERENT  NERVES. 


a  ZhCBXQ 


PRESENTED    TO  THE  BOARD  OF  UNIVERSITY  STUDIES  OF 

THE  JOHNS  HOPKINS  UNIVERSITY  FOR  THE  DEGREE 

OF  DOCTOR  OF  PHILOSOPHY. 


BY 
REID   HUNT,   A.  B. 


REPRINTED  FROM 
THE  JOURNAL   OF   PHYSIOLOGY,  VOL.   XVIIL 

1895. 


QPill 
H9I 


in    [From  the  Journal  of  Physiology.      Vol.  XVIII.  Nos.   b  &  <o,  1895.] 

CQ 


THE  FALL  OF  BLOOD-PRESSURE  RESULTING  FROM 
THE  STIMULATION  OF  AFFERENT  NERVES.  By 
RE  ID  HUNT,  A.B.  Felloiv  in  the  Johns  Hopkins  University. 
(Six  Figures  in  Text.) 

Part  I,    Historical, 

Two  effects  are  commonly  said  to  be  produced  by  the  stimulation  of 
the  central  end  of  a  sensory  nerve — (1)  reflex  constriction  of  many  of 
the  smaller  arteries,  principally  those  supplied  by  the  splanchnic  nerves, 
and  (2)  a  reflex  dilatation  of  others,  especially  those  of  the  skeletal 
muscles  and  of  the  skin\  As  the  effect  of  the  former  is  usually  greater 
than  that  of  the  latter,  the  result  is  a  rise  of  arterial  pressure.  But  a 
different  result  is  often  obtained,  viz,,  a  fall  of  arterial  pressure.  This 
latter  result  seems  to  have  been  first  described  by  E.  Cyon  as  following 
the  stimulation  of  a  sensory  nerve  of  a  rabbit  under  the  influence  of 
chloral. 

The  mechanism  of  the  local  reflex  dilatation  does  not  appear  to  have 
been  very  fully  discussed ;  but  the  statements  usually  made  seem  to 
point  to  the  conception,  that  the  vaso-dilators  of  some  parts  of  the  body 
are  in  some  way  stimulated  reflexly  simultaneously  with  the  vaso- 
constrictors of  other  parts. 

Apparently  no  one  has  studied  the  question  as  to  the  areas  in  which 
the  dilatation  takes  place  when  a  fall  of  arterial  pressure  occurs  as 
described  above: — for  example,  whether  the  dilatation  is  general  or  is 
confined  to  certain  localities;  but  several  physiologists  have  made  a 
study  of  the  afferent  nerves  and  the  centres  concerned,  Cyon  supposed 
a  rise  of  pressure  could  be  obtained  reflexly  only  when  the  cerebral 
hemispheres  were  intact  or  normal ;  if  they  were  removed  or  poisoned 
by  chloral  hydrate,  a  fall  occurred.    Dittmar^  however,  showed  that  the 

^  For  references  to  the  literature  see  Tiger  stedt's  Lehrbiich  d.  Fhysiologie  d.  Kreislaufs. 
Leipzig,  1893,  pp.  518—529. 

^  Dittmar.     Ber.  d.  sachs.  Gesellsch.  d.  Wiss.,  Math.-phys.  CI.,  18.    1870. 

PH,  XVIII.  26 


382  /?.   HUNT. 

pressure  still  rose,  on  stimulation  of  sensory  nerves,  after  the  complete 
removal  of  the  hemispheres. 

The  first  and  apparently  only  thorough  investigation  of  the  afferent 
nerves  concerned  in  this  reflex  was  made  by  Latschenberger  and 
Deahna^  From  a  study  of  the  forms  of  the  curves  of  blood-pressure 
during  stimulation  of  various  afferent  nerves,  from  the  fall  of  pressure 
obtained  by  long-continued  stimulation  of  the  sciatic,  and  especially  from 
the  fail  following  the  removal  of  a  clamp  from  the  femoral  artery,  they 
concluded  that  from  all  the  blood  vessels  of  the  body  depressor  as  well 
as  pressor  nerve-fibres  run  to  the  vaso-motor  centre.  They  thought 
further,  that  when  the  pressure  in  one  vascular  area  was  decreased  {e.rj. 
by  clamping  the  artery)  the  pressor  fibres  were  stimulated  and  a  rise 
occurred,  whereas,  when  the  pressure  is  suddenly  increased  (as  when  the 
clamp  was  removed),  the  depressor  fibres  were  stimulated  and  a  fall  of 
arterial  pressure  resulted.  However,  it  was  soon  shown  by  Zuntz'^  that 
it  was  the  anaemia  of  the  tissues  rather  than  the  pressure  in  the  blood 
vessels  which  caused  the  reflex  rise  of  pressure.  Then  the  failure  of 
several  experimenters  to  find  another  nerve  like  the  depressor,  stimula- 
tion of  which  invariably  caused  a  fall  of  pressure,  lead  some  physiologists 
to  the  view  that  there  are  no  depressor  fibres  in  the  sense  used  by 
Latschenberger  and  Deahna'',  but  that  the  fall  of  pressure  sometimes 
obtained  is  due  to  the  condition  of  the  centred  It  is  true  that  writers 
sometimes  speak  of  "  depressor  "  fibres  in  the  sciatic  and  other  nerves, 
and  Bayliss^  has  recently  put  forward  a  theory  of  their  action,  but  the 
possibility  that  the  fall  of  pressure  in  these  cases  is  due  to  changes  in 
the  centre  was  not  excluded''. 

Howeir  has  recently  published  an  account  of  experiments  made  by 
himself  and  some  of  his  pupils,  on  the  effects  of  cold  upon  the  con- 

1  Latschenberger  and  Deabna.     Pfliiger^s  Archiv,  xn.  157.    1876. 

2  Zuntz.     Pfliiger's  Archiv,  xwi.-kOi.    187H. 

3  Tigerstedt.     Op.  cit.  p.  525. 

*  See  Knoll.  Sitzher.  d.  Akad.  d.  Whs.  z.  Wien,  Math.-naturw.  CI.,  92,  Abtb.  3,  p. 
451.    1885.     Also  Foster,  Tt'-ri-boo;;;  o/P/i?/sio%2/,  6th  ed.  p.  3-45.     1893. 

5  Bayliss.     This  Journal,  xiv.  317.   1893. 

^  After  this  paper  had  been  written  my  attention  was  called  to  a  section  in  the  article 
by  Bradford  and  Dean  on  the  "Pulmonary  Circulation  "  (This  Journal,  xvi.  67.  1894), 
in  which  they  describe  the  effect  of  stimulation  of  the  central  ends  of  the  intercostal  nerves. 
They  state  that  stimulation  of  the  central  ends  of  certain  of  these  nerves  is  followed  by  a 
fall  of  pressure  while  that  of  the  sciatic  is  followed  by  a  rise,  and  argue  from  this  that,  as 
the  vaso-motor  centre  is  in  normal  condition,  the  fall  can  probably  be  explained  only  by 
supposing  that  there  are  two  sets  of  fibres  here— pressor  and  depressor. 

"  Howell,  Budgett  and  Leonard.     This  ./owrHa/,  xvi.  298.   1894. 


AFFERENT  NERVES  ON  BLOOD-PRESSURE.        383 

ductivity  of  nerve  fibres,  in  which  he  shows  that,  if  a  portion  of  the 
sciatic  is  cooled  to  near  0°  C,  and  stimulated  peripherally  to  this  part, 
the  result  is  a  reflex  fall  of  pressure.  He  suggests  that  there  are 
depressor  as  well  as  pressor  fibres  present  and  that  the  former  do  not 
lose  their  power  of  conducting  impulses  at  a  low  temperature  as  readily 
as  do  the  latter. 

Part  II.    The  Afferent  Fibres  by  which  a  Fall  of 
Pressure  is  produced. 

Method  of  experimenting.  In  addition  to  the  method  of  cooling, 
other  methods  were  employed  to  produce  a  reflex  fall  of  blood-pressure ; 
these  will  be  described  in  their  proper  places.  The  animals  used  were 
cats,  dogs,  and  rabbits  and  they  were  in  all  cases  anaesthetized,  by  some 
method.  The  vagi  were  cut  in  most  cases.  The  blood-pressure  was 
taken  from  the  carotid  and  recorded  in  the  usual  manner.  In  most  of  the 
experiments  the  nerve  stimulated  was  the  sciatic,  but  sometimes  the 
saphenous,  ulnar,  median  or  anterior  crural  and  occasionally  other 
nerves  were  used.  I  shall  consider  first  the  stimulation  of  the  sciatic, 
and  then  compare  with  these  results  the  effects  produced  when  the  other 
nerves  were  stimulated. 

1.     Effect  of  Cooling. 

The  nerve  was  cooled  in  the  manner  described  by  Howell^  viz.,  by 
drawing  the  central  end  of  the  divided  nerve  through  the  transverse 
tube  passing  through  the  angle  of  a  V-tube  ;  cold  alcohol  was  circulated 
through  the  V-tube  and  so  around  the  transverse  tube  containing  the 
nerve.  In  this  way  the  nerve  could  readily  be  cooled  to  0°  C.  or  lower. 
No  attempt  was  made  to  determine  the  exact  temperature  of  the 
nerve ;  the  temperature  given  is  that  of  the  alcohol  at  the  angle  of  the 
V-tube  and  as  Howell  showed,  that  of  the  nerve  probably  did  not  vary 
from  this  by  as  much  as  1°  C.  The  nerve  was  stimulated  an  inch  or 
two  below  the  tube  with  a  weak  interrupted  current  from  a  Du  Bois 
Reymond  coil.  As  the  result  varies  with  the  kind  of  anaesthesia 
employed,  it  will  be  best  to  consider  the  different  cases  separately. 

Brain  Compression.  This  was  produced  by  trephining,  care  being 
taken  not  to  rupture  the  dura  mater,  and  then  carefully  pressing  a 
sponge  or  bandage,  moistened  with  a  -GVo  solution  of  sodium  chloride, 
into  the  cavity  of  the  skull  till  anaesthesia  was  complete.     Rabbits  did 

1  Howell.     Op.  cit.  p.  300. 

26—2 


384.  R.   HUNT. 

not  endure  this  operation  very  well  and  in  cats,  with  the  vagi  divided, 
the  curve  of  blood-pressure  was  sometimes  very  irregular  and  difficult 
to  interpret.  The  method  however  often  gave  very  satisfactory  results. 
Howell  gives  what  may  be  considered  a  typical  example  of  the 
reflex  fall  of  pressure  obtained  by  cooling  and  stimulating  the  sciatic 
when  this  method  of  anaesthesia  is  employed.  I  have  nothing  to  add  to 
his  results.  The  effect  is  almost  always  easily  obtained.  The  following 
experiment  may  serve  as  an  example  (see  Fig.  1,  A  and  B): 


I ■      I      f      I       »      I I I I I 1 1 i — I » » » » • — 

A 


_r —^ 


_£_- 


B 
Fig.  1.  Record  from  cat  anaesthetized  by  brain  compression.  Vagi  cut. 
Sciatic  stimulated.  "A"  shows  fall  of  pressure  when  nerve  was  cooled  to 
4A°  C.  "B"  shows  rise  of  pressure  when  nerve  was  stimulated  at  26°. 
Strength  of  stimulus  the  same  in  both  cases.  "  B  "  is  1  minute,  50  seconds 
after  "  A."      Tracing  to  be  read  from  right  to  left.      Time  record  in  seconds. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        385 

Jan.  13th.  Cat;  vagi  cut.  Stimulation  of  the  nerve  with  a  current  a 
little  more  than  just  perceptible  to  the  tongue,  with  the  nerve  at  26°  C.  gave 
a  rise  of  38  mm.  Hg.  The  nerve  was  cooled  to  10°  and  again  stimulated 
with  the  same  current;  there  was  no  effect  on  blood-pressure  or  a  minute 
rise.  The  cooling  was  now  continued  to  4|-°  C;  now  stimulation  was  fol- 
lowed by  a  fall  of  20  mm.;  the  pressure  returning  at  once  after  stimulation 
ceased.  Water  at  about  26°  0.  was  now  circulated  around  the  nerve  and  the 
stimulus  again  applied  110  seconds  after  the  former  one.  A  rise  of  28  mm. 
followed.  Similar  results  were  obtained  in  an  experiment  upon  a  cat 
anaesthetized  by  division  of  the  crura  cerebri. 

Ether.  Ether,  alone  or  with  other  anaesthetics,  has  a  marked 
influence  in  increasing  the  ease  with  which  depressor  effects  are 
obtained.  Very  often  in  experiments  in  which  this  anaesthetic  was 
used,  a  fall  of  pressure  was  the  only  result  from  stimulation  of  the 
sciatic  at  the  temperature  of  the  room.  This  was  especially  the  case 
in  experiments  upon  rabbits.  With  dogs  and  cats,  however,  if  the 
nerve  had  been  freshly  exposed  and  the  stimulating  current  was 
moderately  strong,  a  rise  of  pressure  usually  occurred ;  in  such  cases 
cooling  the  nerve  caused  a  marked  fall  during  stimulation.  If,  how- 
ever, the  current  was  weak  or  if  the  nerve  had  been  exposed  for  some 
time  or  stimulated  frequently,  either  a  fall  of  pressure  resulted  or  no 
change  was  produced,  either  at  the  temperature  of  the  room  or  when 
the  nerve  was  cooled.     Examples  of  such  experiments  are  as  follows : 

Dec.  12th.  Rabbit;  vagi  intact.  With  temperature  at  23°,  a  weak 
stimulus  caused  a  rise  of  19  mm.  ;  the  nerve  was  now  cooled  to  15°  and 
stimulated  with  the  same  current :  a  fall  of  9  mm.  resulted.  Warming  the 
nerve  in  this  experiment  did  not  restore  its  power  to  produce  a  rise  on 
stimulation. 

Dec.  13th.  Dog;  a.c.e.  mixture.  Stimulation,  with  a  weak  current, 
of  the  sciatic  at  the  temperature  of  the  I'oom  caused  no  change  in  the  blood- 
pressure;  with  the  temperature  at  12°,  however,  the  same  current  caused 
a  fall  of  10  mm.  In  this  experiment  weak  stimulation  alone  did  not  cause  a 
fall  of  pressure. 

Aceto7ie  Chloroform  {Trichloride  oj  Acetonic  Acid ').  A  few  experi- 
ments were  made  on  cats  and  dogs  anaesthetized  with  this  drug;  the 
curves  of  blood-pressure  were  remarkably  uniform,  and  a  slight  rise  or 
fall  was  more  conspicuous  and  less  difficult  to  interpret  than  with  many 

1  I  am  indebted  for  this  drug  to  Prof,  Abel,  who  has  been  using  it  for  some  time  in  his 
laboratory  as  an  anesthetic. 


386  R   HUNT. 

other  anaesthetics.  Ou  the  other  hand,  the  vaso-motor  centre  did  not 
seem  to  be  very  irritable  and  the  reflex  changes  of  pressure  were  not 
great.  The  results,  however,  were  similar  to  those  obtained  with  brain 
compression.     The  following  will  serve  as  an  example. 

May  10th.  Cat,  anpesthetized  with  1  Gni.  Acetone  Chloroform.  Vagi 
cut.  Blood-pressure  75  mm.  Hg.,  rising  later  to  100  mm.  With  tempera- 
ture at  26°  and  secondary  coil  at  7  ctm.  from  the  primary,  a  rise  of  7  mm. 
occurred  ;  the  temperature  was  lowered  to  4° :  now  stimulation  with  the 
same  strength  of  current  was  followed  by  a  fall  of  7  mm.  As  the  nerve 
was  warmed  again  stimulation  caused  a  rise ;  at  29°,  coil  7  ctm.,  the  rise 
was  20  mm. 

Curare.  Curare  seems  to  exert  an  opposite  influence  to  that  of 
ether,  i.e.  it  causes  the  pressor  effects  to  be  more  marked.  No  fall  of 
blood-pressure  could  be  obtained  by  stimulating  the  cooled  sciatic  in 
curarized  cats  or  rabbits  when  ether  had  been  given  or  the  brain  com- 
pressed, or  in  dogs  to  which  morphia  and  curare  had  been  given  \ 

In  one  experiment  upon  a  cat  with  curare  and  brain  compression, 
no  fall  of  pressure  could  be  obtained  on  cooling,  but  on  injecting  3  c.cm. 
of  a  10  7o  solution  of  chloral  hydrate  into  the  external  jugular  vein, 
stimulation  of  the  sciatic  readily  caused  a  fall  of  pressure  when  the 
nerve  was  cooled  to  10°  C.  or  below. 

In  many  cases,  especially  at  the  beginning  of  an  experiment,  the 
rise  of  pressure  was  followed  soon  after  stimulation  ceased,  by  a  very 
marked  fall.     This  result  will  be  discussed  later. 

Ulnar  and  Median.  A  few  experiments  were  made  upon  these 
nerves  in  dogs  and  cats ;  the  same  results  were  obtained  as  with  the 
sciatic,  viz.  a  rise  at  high  temperatures  and  a  fall  at  lower  ones. 

Saphenous  Nerve.  In  rabbits  and  dogs  a  fall  of  pressure  can  be 
obtained  from  this  nerve  on  cooling,  as  easily  as  from  the  sciatic ;  also 
in  animals  anaesthetized  with  ether  or  chloroform,  a  very  marked  fall 
sometimes  results  from  stimulation.  The  saphenous  nerve  of  the  cat 
seems  to  differ  markedly  in  this  respect  from  that  of  the  rabbit  or  dog. 
For  in  this  animal  a  fall  of  pressure  rarely  occurred  from  stimulation  of 
the  saphenous  whatever  the  anaesthetic,  or  the  temperature  or  the 
strength  of  the  stimulus.  In  the  same  individual  cooling  and  stimu- 
lating the  sciatic  often  gave  a  fall  of  pressure,  while  similar  treatment 
of  the  saphenous  was  without  effect.     So,  too,  in  animals  anaesthetized 

1  Griitzner  failed  to  obtain  fall  of  blood-pressure  from  cooling  and  stimulating  the 
sciatic  of  a  curarized  dog.     PJHiger's  Archiv,  xvii.  215.    1878. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        387 

with  ether,  the  saphenous  gave  either  a  rise  or  no  effect,  while  the 
sciatic  often  gave  a  fall  of  pressure.  Thus  there  seems  to  be  a  real 
difference  between  this  nerve  and  those  so  far  considered.  In  this 
connection  the  statement  of  Knoll  that  a  fall  of  pressure  sometimes 
results  from  stimulation  of  most  afferent  nerves,  with  the  exception  of 
the  splanchnic  ^  is  of  interest ;  also  the  observation  of  Bradford^  that 
a  fall  of  pressure  sometimes  occurs  on  stimulating  the  intercostals. 

2.    Effect  of  stimulating  the  central  end  of  a  recently- 
regenerated  nerve. 

A  few  experiments  were  made  to  determine  whether,  in  the  regene- 
rating sciatic,  any  difference  in  the  time  of  return  of  the  different 
reflex  vaso-motor  functions  could  be  observed,  or,  stating  the  problem 
in  the  terms  of  the  hypothesis  that  there  are  two  sets  of  fibres,  pressor 
and  depressor,  whether  one  set  regenerates  earlier  than  the  other. 
This  work  was  suggested  to  me  by  some  observations  of  Professor 
Howell's  on  the  regeneration  of  vaso-motor  nerves;  he  found  that  the 
dilators  regenerate  earlier  than  the  constrictors. 

The  animals  chosen  for  these  experiments  were,  with  one  exception, 
cats ;  one  sciatic  was  crushed  by  drawing  a  ligature  tightly  around  it, 
high  in  the  thigh ;  the  wound  was  closed  with  aseptic  precautions  and 
the  nerve  allowed  to  regenerate.  When  signs  of  sensation  and  motion 
became  apparent  for  some  distance  down  the  leg,  that  is,  after  the 
lapse  6f  five  or  six  weeks,  the  animal  was  experimented  upon ;  both 
sciatics  (the  regenerating  and  the  normal)  were  cut  and  their  central 
ends  stimulated  alternately,  and  the  effect  upon  the  blood-pressure 
recorded  on  the  kymograph.  In  all  but  one  experiment  there  was 
distinct  evidence  that  the  depressor  effect  returned  first ;  the  exception 
being  an  experiment  upon  a  cat  made  forty-eight  days  after  the  nerve 
was  crushed.  This  was  the  longest  period  allowed  to  elapse  between 
crushing  the  nerve  and  making  the  experiment  and  the  part  of  the 
nerve  stimulated  gave  the  same  results  as  the  normal  nerve,  viz.  a  rise 
of  blood-pressure.  It  is  very  probable  that  if  the  nerve  had  been 
cut  lower  down  and  stimulated,  the  usual  result  would  have  been 
obtained,     A  few  details  of  some  of  the  experiments  will  be  given, 

June  26,     Cat.     Left  sciatic  crushed   39  days  previously,     Ansesthesia 
was  produced  by  brain  compression  and  the  two  sciatics  prepared  for  stimu- 

1  Knoll,      Sitzber.  d.  Akad.  d.  Wiss.  za  Wien,   Math.-naturw.  CL,   92,  Abth.  3,  p. 
449.    1885. 

2  Bradford.     This  Journal,  x,  397.    1887, 


388  .  R.   HUNT. 

latiou.  Stimulation  of  the  left  nerve  with  the  coil  at  8^  ctm.,  a  weak 
stimulus,  caused  a  slight  fall  of  pressure  ;  the  coil  was  moved  up  to  7  and 
then  to  4  ctm.;  falls  of  pressure  of  8  and  10  mm.  respecti^'ely  occurred. 
Stimulation  of  the  right,  i.e.  the  normal  sciatic,  with  the  coil  at  8  ctm.  gave  a 
rise  of  pressure  of  40  mm.  These  results  were  constant  and  obtained  both 
before  and  after  section  of  the  vagi.     (Fig.   2,  A  and  B.) 


.^^^^"^r 


B 

Fig.  2.  Cat.  Brain  compres.sed.  Vagi  intact.  Left  sciatic  crushed  39 
days  previously.  "A"  shows  fall  of  pressure  from  stimulation  of  regenerating 
sciatic.  "B"  shows  rise  of  pressure  and  slowing  of  heart  from  stimulation  of 
normal  sciatic.     Tracing  from  right  to  left. 

Dec.  12th.  Cat.  Left  sciatic  crushed  38  days  previously.  Anajsthesia 
produced  by  ether.  Vagi  intact.  Stimulation  of  the  normal  nerve  gave  a 
rise  of  16  mm.;  the  same  current  applied  to  the  left  caused  a  fall  of  12  mm. 
The  maximum  fall  of  pressure  in  this  case  was  obtained  by  stimulating  the 
nerve  immediately  below  the  point  where  the  ligature  had  been  applied. 

Another  experiment  shows  a  gradual  transition  in  the  effect  upon 
the  vaso-motor  centre  from  stimulation  of  the  nerve  at  points  more  and 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        389 

more  towards  the  periphery.  When  the  stimulus  was  applied  to  a 
point  near  the  wound  there  was  a  rise  of  pressure ;  a  little  lower,  a  fall 
occurred.  As  the  nerve  was  stimulated  still  more  peripherally  the 
effect  became  less  and  less,  and  finally  a  point  was  reached  where  it 
seemed  entirely  unirritable, — at  least  as  far  as  its  influence  on  the 
vaso-motor  centre  was  concerned.  Another  experiment  showed  the 
same  difference  between  the  normal  and  regenerated  nerve  in  a  slightly 
different  way.  In  this  experiment  stimulation  of  both  the  normal  and 
regenerating  nerve  caused  a  fall  of  pressure  when  the  current  was 
weak ;  the  strength  of  the  stimulus  was  now  increased :  the  regene- 
rating nerve  continued  to  cause  a  reflex  fall  of  pressure  while  the 
normal  one  caused  a  rise.  Results  entirely  similar  to  the  above  were 
obtained  in  an  experiment  upon  a  dog  in  which  one  sciatic  had  been 
crushed  38  days  previously. 

An  experiment  was  also  made  upon  the  saphenous  nerve  of  a  cat. 
Stimulation  of  the  regenerating  nerve  42  days  after  it  was  crushed,  at, 
and  just  below  the  point  where  the  ligature  had  been  applied,  caused  a 
rise  of  pressure ;  when  applied  to  a  still  lower  point,  stimulation  was 
without  effect.  In  no  case  did  a  distinct  fall  of  pressure  result  from 
stimulation  of  this  nerve,  as  was  the  rule  with  the  regenerating  sciatic. 
This  is  the  result  we  should  expect  when  we  remember  that  a  fall  of 
pressure  from  stimulation  of  the  saphenous  is  very  unusual. 

3.     Mechanical  stimulation  of  muscles. 

Kleen^  has  shown  that  if  a  purely  muscular  stimulation  be  pro- 
duced by  kneading  the  muscles  of  a  rabbit's  leg,  a  fall  of  blood-pressure 
results;  Brunton  and  Tunnicliffe^  have  obtained  similar  results.  I 
repeated  this  experiment  on  cats  and  rabbits  and  found  that  here  also 
the  anesthetic  had  a  marked  influence  on  the  result. 

With  curarized  cats,  morphia  also  being  given  or  the  brain  com- 
pressed, kneading  the  muscles  of  a  limb  invariably  caused  a  fall  of 
blood-pressure.     The  following  will  serve  as  an  example. 

Feb.  2nd.  Cat.  Morphia  and  curare ;  vagi  cut.  Kneading  the  muscles 
of  the  leg,  from  which  the  skiu  had  been  removed,  caused  a  fall  of  pressure  of 
10  mm.,  after  which  the  pressure  slowly  returned. 

With  brain  compression  alone,  kneading  the  muscles  usually  gave  a 
fall  of  pressure,  but  the  results  were  not  so  marked  or  so  invariable  as 

^  Kleen.     Skandinav.  Archiv  f.  Physiol,  i.  2^7.    1887. 

2  Brunton  and  Tunnicliffe.     This  Journal,  xvii.  373.     1894. 


390  R   HUNT. 

with  curare.  With  ether  the  results  were  still  less  marked  ;  and  one 
or  two  experiments  on  cats  anaesthetized  with  acetone  chloroform  gave 
negative  results.  The  fact  that  a  fall  of  blood-pressure  could  be  so 
easily  brought  about  by  kneading  the  muscles,  if,  at  the  same  time, 
care  was  taken  to  avoid  rubbing  the  skin,  suggested  that  direct 
electrical  stimulation  of  the  nerves  to  the  muscles,  or  of  the  muscles 
themselves,  would  also  cause  a  fall.  This  supposition,  however,  was 
shown  by  experiment  to  be  incorrect.  The  nerves  investigated  were 
branches  of  the  sciatic  and  anterior  crural,  and  subsequent  dissection 
showed  them  to  be,  in  large  part  at  least,  muscular ;  stimulation  of 
these,  with  weak  or  strong  interrupted  currents,  was  always  followed  by 
a  rise  of  pressure.  Direct  electi'ical  stimulation  of  the  muscles  by 
plunging  the  electrodes  into  them  also  gave  a  rise,  while  kneading 
them  caused  a  fall  of  pressure. 

4.     Weak  electrical  stimulation. 

Knoll  ^  remarks  that  he  received  the  impression  from  his  experi- 
ments, that  a  depressor  effect  was  usually  the  result  of  a  weak 
stimulation,  while  the  pressor  effect  followed,  as  a  rule,  a  stronger 
stimulus. 

I  often  noticed  the  same  difference ;  sometimes  it  was  very  marked. 
For  example,  in  an  experiment  upon  a  cat  ansesthetized  by  brain  com- 
pression, stimulation  of  the  sciatic  with  the  secondary  coil  at  10  ctm, 
from  the  primary,  caused  a  fall  of  12  mm.;  with  the  coil  at  7  ctm.,  on 
the  other  hand,  there  was  a  rise  of  16  mm. 

5.     Effect  of  repeated  stimulation,  of  exposure,  &c. 

Latschenberger  and  Deahna-  observed  that  after  the  sciatic  had 
been  stimulated  repeatedly,  a  point  was  reached  when  a  fall  of  pressure 
took  the  place  of  the  usual  rise. 

According  to  their  theory  the  pressor  fibres  fatigued  earlier  than  the 
depressor.  Their  experiments  were  made  upon  curarized  animals.  I 
have  often  obtained  the  same  results,  but  far  more  readily  on  animals 
ansesthetized  by  brain  compression.  The  following  experiments  will 
illustrate  this  point. 

Dec.  30tb.  Cat  anaesthetized  by  brain  compression.  Stimulation  of  the 
sciatic  nerve  with  a  weak  current  caused,  in  the  early  part  of  the  experiment, 

1  Knoll.     Op.cit.  p.  451. 

'•'  Latschenberger  and  Deahna.     Op.  cit.  pp.  165—6. 


AFFERENT  NERVES  ON  BLOOD-PRESSURE.        391 

a  veiy  considerable  rise,  of  pressure ;  soou  however  a  strong  stimulus  was 
required  to  produce  this  effect,  a  weak  one  causing  now  a  fall.  After  one  stimu- 
lation with  a  weak  current,  with  the  temperatiire  at  24°  C,  the  fall  was  24  mm. ; 
the  wound  was  then  closed  and  the  animal  left  undisturbed  for  an  hour.  The 
blood-pressure  fell  considerably  during  this  time,  but  otherwise  the  condition 
of  the  cat  seemed  to  have  remained  unchanged.  At  the  end  of  the  hour  the 
sciatic  was  stimulated  with  the  same  strength  of  cui'rent  and  at  the  same 
temperature  as  before ;  the  result  was  a  rise  of  pressure  of  38  mm. 

It  might  be  objected  to  this  experiment  that  the  long  interval 
between  the  stimulations  had  permitted  some  change  to  occur  in  the 
centres  themselves.  A  second  experiment  will  therefore  be  described  to 
which  this  objection  cannot  be  made. 

Jan.  10th.  Cat ;  brain  compression  and  light  etherization.  The  right 
sciatic  was  exposed,  but  some  difficulty  was  experienced  in  getting  it  properly 
adjusted  in  the  cooling  tube ;  consequently  the  nerve  was  exposed  to  the  air 
for  some  time  and  rather  roughly  treated.  Stimulation  of  this  nerve  with 
currents  of  moderate  strength  caused  only  a  fall  of  pressure.  The  left  sciatic 
was  now  quickly  exposed  and  stimulated  with  a  current  of  the  same  strength 
as  that  employed  for  the  right  nerve  ;  a  rise  of  pressure  was  the  invariable 
result. 

Unless  we  make  the  assumption  that  stimulation  of  the  two  sciatics 
may  normally  be  followed  by  different  results,  this  experiment  can 
scarcely  be  explained  otherwise  than  by  supposing  the  rough  treatment 
and  exposure  of  the  right  sciatic  to  have  made  it  incapable  of  conducting 
or  developing  pressor  impulses  as  readily  as  depressor. 

Another  difference  between  the  vaso-motor  reflexes  obtained  fcom 
curarized  animals,  and  from  those  anaesthetized  by  ether  or  brain  com- 
pression, may  be  mentioned  in  this  connection.  It  often  happened  that 
the  rise  of  pressure,  following  stimulation  of  the  sciatic  of  curarized 
animals,  was  followed,  after  stimulation  ceased,  by  a  very  considerable 
fall.  Later  in  the  experiment,  no  such  succeeding  fall  of  pressure  occurred 
although  the  rise  was  as  great  as  before ;  indeed  the  pressure  often 
remained  above  the  previous  level  for  some  time.  With  animals  under 
ether,  a  phenomenon  opposite,  in  a  certain  sense,  to  this  occurred ;  the 
first  few  stimulations  caused  a  rise  of  pressure,  while  later  only  a  fall 
occurred.  Another  kind  of  after-effect  was  sometimes  observed  on  cats 
ansesthetized  by  brain  compression.  For  example,  in  the  early  part  of 
one  experiment,  no  fall  of  pressure  occurred  after  the  rise  from  stimula- 
tion of  the  sciatic ;  later  there  was  invariably  such  a  fall  of  pressure. 


392  A'.   HUNT. 

These  results  will  be  referred  to  later  in  speaking  of  the  action  of  curare 
and  ether. 


6.     Effect  upon  the  blood-pressure  of  closing  and  opening 
a  vascular  area. 

Latschenberger  and  Deahna  laid  considerable  stress  upon  the 
phenomena  resulting  from  closing  and  opening  a  vascular  area.  As 
described  above,  they  found  that  a  rise  of  pressure  followed  the  clamping 
of  an  artery,  and  a  fall,  greater  than  could  be  accounted  for  on  purely 
mechanical  principles,  occurred  when  the  clamp  was  removed.  They 
attributed  these  results  to  the  stimulation  of  pressor  and  depressor 
nerves  respectively  of  the  vessels  of  the  area  to  which  the  arteries  were 
distributed. 

As  far  as  I  am  aware  no  one  has  repeated  the  experiments  with 
reference  to  the  fall  of  pressure  and  it  seemed  desirable  therefore  to  do 
so.  I  think  the  results  obtained  agree  with  those  described  by  the 
above  writers,  but  as  they  were  not  invariably  obtained  and  were  not 
marked,  the  experiments  were  not  continued.  The  following  will  serve 
as  an  example. 

Cat,  aneesthetized  by  ether;  the  sciatic,  anterior  crural  and  saphenous 
nerves  were  cut  on  the  right  side  ;  those  of  the  left  were  intact.  When 
the  right  common  iliac  artery  was  clamped,  the  pressure  in  the  carotid 
rose  10  mm.  and  remained  at  that  height  till  the  clamp  was  removed, 
when  it  returned  to  just  the  level  it  occupied  before.  A  rise  of  pressure 
would  of  course  be  expected  when  a  tolerably  large  vascular  area  is 
suddenly  closed.  And  further  we  should  expect  a  greater  rise  to  follow 
the  closing  of  arteries  which  were  dilated  from  section  of  their  nerves, 
than  from  those  whose  nerves  were  intact.  And  this  is  what  was  found; 
for  the  immediate  rise  following  the  clamping  of  the  left  common  iliac 
artery  was  extremely  slight.  In  the  course  of  a  minute  and  a  half  the 
pressure  rose,  however,  6  mm.  This  rise  cannot  be  explained  on 
mechanical  grounds  since  it  did  not  occur  on  the  sides  where  nerves  had 
been  cut.  It  is  probably  due  as  explained  by  Latschenberger  and 
Deahna,  to  a  stimulation  of  pressor  nerves,  not  as  they  thought,  by  the 
collapse  of  the  arteries,  but  by  the  local  anaemia  as  described  by  Zuntz. 
The  clamp  was  now  removed  from  the  left  artery  and  another  placed 
simultaneously  upon  the  right ;  the  rise  of  pressure  in  this  case  was  but 
5  mm.  or  one  half  as  great  as  above.  Latschenberger  and  Deahna 
observed  an  actual  fall  in  such  cases.     The  explanation  of  this  is  pro- 


AFFERENT  NERVES   ON  BLOOB-PRESSURE.         393 

bably  the  one  given  by  Latschenberger  and  Deahna;  that  is,  that 
the  sudden  distention  of  the  artery  (or  the  sudden  inrush  of  oxygenated 
blood,  by  which  the  local  anaemia  was  relieved),  stimulated  depressor 
fibres  and  so  the  mechanical  effect  of  simultaneously  closing  the  right 
artery  was,  to  a  certain  extent,  counterbalanced. 

This  hypothesis  is  made  more  plausible  by  similar  results  obtained 
by  a  slightly  different  method,  which  seems  less  open  to  objection.  As 
described  above,  the  removal  of  the  clamp  from  the  artery  on  the  side 
whose  nerves  were  cut,  was  followed  by  a  simple  return  of  the  pressure 
to  the  original  level;  removal  of  the  clamp  from  the  side  with  the  nerves 
intact,  was  followed  by  a  fall  below  the  original  level.  In  some  cases 
the  fall  was  as  much  as  13  mm.  Section  of  the  nerves  on  this  side 
caused  the  difference  to  disappear. 

7.     Negative  results. 

In  addition  to  the  various  forms  of  stimulation  described  above,  two 
others  were  tried  in  the  hope  that  some  separation  of  the  pressor  and 
depressor  effect  might  be  obtained.  They  gave  negative  results,  but  I 
shall  refer  to  them  briefly. 

Different  rates  of  electrical  stimulation.  Rhythmic  stimulation  of 
the  sciatic  was  tried  with  the  thought  that  perhaps  some  such  separa- 
tion of  pressor  and  depressor  effect  might  be  produced,  as  has  been 
described  for  the  peripheral  constrictors  and  dilators  by  Ostroumoff^ 
and  especially  by  Bowditch  and  Warren  ^  but  the  result  was  negative. 
The  nerve  was  stimulated  with  an  induced  current ;  the  current  of  the 
primary  circuit  was  interrupted  at  different  rates,  from  once  in  two 
seconds  to  sixty  times  per  second.  Only  a  rise  of  pressure  resulted,  the 
character  of  which  was  determined  by  the  number  and  strength  of  the 
stimuli ;  the  rise  was  very  gradual  with  slow  weak  stimulation,  but  took 
place  much  more  suddenly  with  stronger  and  more  rapid  stimulation. 

Chemical  Stimulation.  It  seemed  possible  that  some  chemical  sti- 
mulus might  be  found  which  would  have  the  effect  of  causing  a  fall 
of  pressure  when  applied  to  an  afferent  nerve.  A  few  salts,  acids,  and 
alkalis  were  therefore  tried,  but  as  yet  no  form  of  chemical  stimulus  has 
been  found  which  seems  to  be  capable  of  giving  a  depressor  effect.  As 
very  little  work   has  been  done  on   the  effect   upon  blood-pressure  of 

1  Ostroumoff.     Pjluger's  Archiv,  xii.  228.    1876. 

2  Bowditch  and  Warren.     This  Journal,  vii.  432.    1886. 


394 


R.   HUNT. 


chemical  stimulation  of  afferent  nervesS  it  may  be  of  interest  to  include, 
in  the  form  of  a  table,  my  chief  results. 

The  substances  whose  action  was  to  be  studied,  were  applied  in 
equimolecular  solutions  to  the  central  end  of  the  divided  sciatic  by 
means  of  a  camel's  hair  brush.  After  each  application  the  chemical  was 
washed  off  with  a  "GYo  NaCl  solution,  a  small  piece  of  the  nerve  cut 
oft'  and  another  application  made. 

I.  Feb.  13th.  Cat,  anaesthetized  by  ether.  Blood-pressure  184  mm.  Hg. 
The  stimulus  was  allowed  to  remain  on  the  nerve  in  each  case  for  25-45 
seconds. 


Stimulus 

Vo  sol. 

Result 

KCl 

3-72 

Ri 

ise  of 

pr 

essure  of  11  mm. 

Induced 

cun 

•ent 

J) 

(very  slight) 

KBr 

5-74 

jj 

10  mm. 

KI 

8-28 

>> 

4  mm. 

NaOH 

1 

>> 

6  mm. 

KOH 

1-4 

)5 

10  mm. 

HNO, 

1 

)j 

10  mm. 

H„SO. 

1 

J) 

15  mm. 

0 


Induced  current  (moderately  strong) 
HCl  1 

I 

Curare  was  now  given  and  the  stimulus  applied  to  the  saphenous  nerve. 
NaCl  5  -84  Rise  of  pressure  1 2  mm. 


Rise   of    pressure      7  mm. 
„     (slight) 


KCl 

NaOH 

KOH 

NaOH 

KOH 


3-72 
1 

1-4 
1 

1-4 


14  mm. 
11  mm. 
8  mm. 
11  mm. 
10  mm. 


The  vagi  were  now  divided  and  the  stimulus  applied  to  the  central  end  of 
one  of  tliese  nerves. 

Induced  current  (moderately  strong)        Fall  of  pressure    8  mm. 
HNO,  17o  Rise  „  24  mm. 

II.     March  28th.     Cat,  anaesthetized  by  ether.     The  experiment  was  made 
in  the  same  manner  as  the  ahove. 


Stimulus  %  sol.  Nerve 

CaCL  11-1  L.  Sciatic 

Induced  current  (weak)  „ 


Effect  on  blood-pressure 
0 
Rise  (very  slight) 


^  See  Griitzner.     PJliifjer's  Archiv,  lviii.  71.    1894. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE. 


395 


stimulus 

0/0  sol. 

Nerve 

Effect  on  blood-pressure 

MgSO, 

12 

L.  Sciatic 

Fall,  followed  by  slight  rise 

MgCl, 

16 

j> 

>>              J)             >} 

CuiTent  (moderate) 

5> 

Rise  of  14  mm. 

BaCl, 

J> 

Rise  of     7  mm. 

KC163 

12-25 

5J 

Rise,  followed  by  fall 

HNO3 

1 

» 

Fall,  followed  by  rise 

Current  (moderate) 

)> 

Rise  of  7  mm. 

Na^SO^ 

U-0 

L. 

Saphenous 

Induced  current  (moderate) 

>} 

Rise  of  8  mm. 

ZnSO^ 

16-1 

>j 

Rise 

CuSO^ 

15-9 

L. 

Anterior 
crural 

'} 

Fall  of  8  mm. 

Induced  current  (moderate) 
KOH  l-i 

Coil 

Curare  was 

Induced  current  (strong) 
NaOH  1 

Induced  current  (weak) 


KCIO,, 


12-25 


,,  Rise  of  8  mm. 

,,  Rise  of  Sh  mm. 

,,  Fall,  followed  by  a  rise 

now  given  and  the  vagi  cut. 

R.  Vagus         Fall  of  8  mm. 

„  Rise  of  4  mm. 

„  Fall  of  11  mm. 

R.  Sciatic        Rise  of  17  mm. 

„  Rise  of  16  mm.  followed  by 

fall  of  24  mm. 


These  experiments  though  very  incomplete  bring  out  one  point  of 
interest,  viz.,  the  difference  which  is  sometimes  observed  between 
chemical  and  electrical  stimulation.  Thus  in  the  first  of  the  above 
experiments  the  sciatic  readily  gave  a  rise  of  pressure  on  stimulation 
with  various  chemical  agents  while  electrical  stimulation  was  ineffective; 
in  the  second,  on  the  other  hand,  the  latter  stimulus  was  the  more  effec- 
tive. A  1 7o  solution  of  HNO3,  for  example,  when  applied  to  the 
sciatic  in  the  former  case,  produced  a  rise  of  10  mm.,  while  a  moderately 
strong  electrical  stimulus  was  without  effect ;  in  the  second  experiment, 
a  solution  of  HNO3  of  the  same  strength,  produced  a  slight  fall  of 
pressure,  though  a  weak  electrical  stimulation  was  followed  by  a  rise  of 
7mm.  The  difference  is  more  marked  in  the  case  of  the  vagi.  In  both 
of  the  above  experiments,  electrical  stimulation  of  various  strengths 
invariably  caused  a  fall  of  pressure,  while  HNO3  and  NaOH  produced 
a  rise.  (See  Fig.  3,  A  and  B.)  In  one  case  the  rise  was  24  mm.  In  an 
experiment  upon  a  dog  a  fall  of  pressure  (11  to  12  mm.)  followed  stimu- 
lation of  the  vagus  by  both  the  induced  current  and  HNO3  (iVo  solution). 


306 


/?.    HUNT. 


y^^/VvnAr-^ 


r\.  t'^- 


'v/^\ 


ftitltttllttltltlttllttLllllttl 


/' 


/ 


I     t     I     »     t     t     t     I     I     I     I     i     t     I     I     I     I     t     I     t     t     t     t     t     I     t     I     I     I     t     I     I 


J 


\ 


B 

Fig.  3.  Cat.  Ether  and  Curare.  Vagi  cut.  "  A  "  shows  fall  of  arterial 
pressure  from  stimulation  of  central  end  of  vagus.  "  B  "  shows  rise  of  pressure 
from  stimulating  vagus  with  HNO^  (P/o)-     Tracing  from  right  to  left. 

So  far  as  these  experiments  go,  I  think  they  show  that  the  effects  of 
both  electrical  and  chemical  stimulation  vary  with  the  condition  of  the 
animal,  but  that  they  vary  independently.  These  differences  do  not 
seem  to  be  entirely  due  to  differences  in  the  strength  of  the  stimuli. 


AFFERENT  NERVES  ON  BLOOD-PRESSURE.        397 

Path  in  the  cord  of  the  afferent  fibres  causing  a  fall  of  pressure.  It 
seems  possible  that  if  the  afferent  fibres,  by  which  a  reflex  fall  of 
pressure  is  brought  about,  are  anatomically  distinct  from  those  which 
cause  the  usual  rise  of  pressure,  that  the  former  may  have  a  separate 
path  in  the  spinal  cord.  The  pressor  fibres  from  the  sciatic  were  shown 
by  Dittmar^  to  run  largely  in  the  lateral  columns,  that  is,  in  the  part 
of  the  cord  in  which  the  nerves  giving  rise  to  sensations  of  pain  are 
supposed  to  run.  It  was  suggested  by  Professor  Howell  that,  as  the 
depressor  effects  were  so  easily  obtained  from  stimulation  of  the 
muscles,  the  afferent  fibres  might  be  those  giving  rise  to  the  muscular 
sense.  If  this  supposition  is  true  we  should  expect  section  of  the 
posterior  columns,  in  which  part  of  these  fibres  are  known  to  run,  to 
block,  to  some  extent,  depressor  influences  coming  from  the  sciatic ; 
and  we  should  further  expect  stimulation  of  these  columns  to  produce  a 
fall  of  pressure.  Neither  of  these  suppositions,  however,  can  be  con- 
sidered as  satisfactorily  demonstrated.  In  regard  to  the  second  point, 
it  may  be  said  that  stimulation  of  the  posterior  columns  gives  usually, 
not  a  fall,  but  a  slight  rise  of  pressure.  The  effect  of  section  of  the 
posterior  columns  upon  vaso-motor  reflexes  is  likely  to  prove,  under 
any  circumstances,  a  difficult  problem.  For  apart  from  questions  of 
shock,  and  the  fact  that  many  of  the  fibres  of  the  muscular  sense  are 
supposed  to  run  in  other  parts  of  the  cord,  there  is  clear  evidence  that 
a  reflex  fall  of  pressure  may  be  obtained  through  the  cord  itself  at 
different  levels.  And,  as  a  matter  of  fact,  some  of  my  experiments 
show  a  reflex  fall  of  pressure  on  stimulation  of  the  sciatic  after  section 
of  the  posterior  columns,  though  this  fall  was  not  greater  than  could  be 
obtained  when  the  entire  cord  was  divided.  On  the  other  hand  it  was 
noticed  several  times  that  after  the  spinal  canal  was  opened  and  the 
posterior  columns  exposed,  a  fall  of  pressure  from  stimulation  of  the 
sciatic  was  less  easily  obtained  than  before.  As  the  posterior  columns 
were  the  parts  most  subjected  to  exposure  and  injury,  this  may  perhaps 
be  taken  to  indicate  that  they  are  the  paths,  in  part,  of  the  afferent 
impulses.  In  any  case,  it  is  interesting  that  after  injuries  to  the  cord, 
pressor  effects  are  usually  more  marked,  while  after  injuries  to  the 
brain  the  opposite  seems  to  be  the  usual  result. 

^  Dittmar.     Ber.  d.  s'dchs.  Gesellsch.  d.  Wiss.,  Math.  phys.  CI.  1873,  p.  455. 


PH.  XVIII.  27 


398  R.  HUNT. 

Part  III.    On  the  local  action  of  depressor  nerve-fibres, 

A  number  of  experiments  were  made  to  determine,  if  possible,  the 
vascular  area  in  which  the  dilatation  occurred  which  was  the  cause  of 
the  fall  of  arterial  pressure  described  above. 

It  was  obviously  impossible,  from  the  manner  in  which  these 
experiments  were  made,  to  determine  the  effect  on  the  vascular  area 
corresponding  to  the  nerves  stimulated,  for  the  efferent  nerves  were 
cut.  However  the  case  may  be  in  the  normal  animal,  it  is  clear  that  in 
these  cases  the  dilatation  occurred  elsewhere  than  in  the  areas  supplied 
by  the  afferent  nerves.  It  was  assumed  that  the  area  most  probably 
involved  in  the  dilatation  was  either  the  corresponding  area  of  the 
other  side  or  the  splanchnic  system,  since  this  is  known  to  play  such  an 
important  part  in  most  vaso-motor  phenomena.  Accordingly  these  two 
areas  were  investigated. 

Method.  At  first  sight  the  most  satisfactory  method  of  inves- 
tigating this  problem  seemed  to  be  the  plethysraographic.  Curare, 
however,  is  almost  always  necessary  in  such  work,  and  this  drug  is,  as 
has  been  shown  above,  distinctly  antagonistic  to  a  reflex  fall  of  pressure 
from  stimulation  of  sensory  nerves.  It  is  obvious,  therefore,  that  the 
plethysmograph  is  not  applicable  to  this  work  and  accordingly  other 
methods  were  tried ;  of  these  the  determination  of  the  venous  pres- 
sure in  different  areas  proved  the  most  satisfactory  and  easiest  of 
application. 

The  method  employed  was  essentially  that  described  by  BayTiss 
and  Starling ^  An  ordinary  Franyois-Franck  cannula  was  used,  into 
the  horizontal  limb  of  which  a  fine  pipette  was  introduced  so  that  it 
reached  just  into  the  neck  of  the  cannula.  The  vertical  limb  was 
connected  with  a  water  manometer  made  of  barometer  tubing ;  a  glass 
T  tube  was  introduced  into  the  rubber  tube  making  this  connection. 
When  the  vein  was  clamped,  a  stream  of  soda^  could  by  this  arrange- 
ment be  led  from  the  pressure  bottle  down  into  the  neck  of  the  cannula 
and  out  through  the  vertical  limb  of  the  T.  The  blood  in  the  cannula 
could  thus  be  washed  out  and  all  trouble  from  clotting  avoided. 

1  Bayliss  and  Starling.     This  Journal,  xvi.  162.   1894. 

2  The  solution  of  soda  used  in  both  the  venous  and  arterial  cannulse  was  the  mixtnre 
of  the  carbonate  and  bicarbonate  proposed  by  Klemensiewicz  {Sitzber.  d,  Akad.  d.  Wiss. 
z.  Wien,  Math.-naturw,  CI.  94,  Abth.  3,  pp.  24 — 6, 1886).  I  have  found  this  solution  much 
more  satisfactory  than  the  solutions  of  MgSO^  and  NaXOj  commonly  employed  in  the 
laboratory.  The  proportions  are  as  follows :  Distilled  Water  4000  c.c,  HNaCOj  186  gm. 
NajCOj  286  gm. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        399 

The  veins  in  which  the  pressure  was  determined  by  this  method 
were  the  portal,  femoral,  and  saphena.  For  determining  the  portal 
pressure  the  cannula  was  introduced  into  the  central  end  of  one  of  the 
splenic  veins.  In  the  case  of  the  femoral  or  saphena  the  cannula  was 
put  into  a  small  branch,  preferably  into  one  joining  the  main  trunk  at 
a  right  angle.  If  a  nerve  in  one  leg  was  to  be  stimulated,  it  is 
to  be  understood  that  the  cannula  was  in  a  vein  of  the  leg  of  the 
opposite  side. 

Before  describing  the  results  of  these  experiments  a  word  may  be 
said  concerning  the  interpretation  of  changes  in  the  portal  pressure. 
So  little  is  known  of  the  action  of  the  constrictors  of  the  portal  vein 
— to  what  extent  and  under  what  circumstances,  for  example, — they  are 
stimulated  reflexly,  that  one  must  be  very  cautious  in  drawing  con- 
clusions from  changes  of  pressure  here. 

Thus  it  is  conceivable  that  both  the  arteries  to  the  viscera  and  the 
branches  of  the  portal  vein  should  be  constricted  or  dilated  simul- 
taneously. In  this  case  there  would  be  a  rise  or  fall  of  arterial  pressure 
with  perhaps  little  or  no  change  in  portal  pressure.  On  the  other  hand 
a  rise  of  portal  pressure  might  mean  a  dilatation  of  the  arteries  or  a 
constriction  of  the  portal  vein  and  its  branches  in  the  liver.  A  fall  of 
pressure  might  be  ascribed  either  to  a  constriction  of  the  arteries  or  to 
a  dilatation  of  the  veins.  Perhaps  there  may  be  combinations  of  these 
effects.  These  possibilities  show  the  difficulty  of  dealing  with  this 
subject;  still  the  results  are  of  value  when  simultaneous  records  of 
changes  of  pressure  in  other  parts  of  the  vascular  area  are  taken. 

Results.  The  results  of  these  experiments  on  venous  pressure  may 
be  stated  very  briefly.  It  was  found  that  in  nearly  every  case  a  fall  of 
arterial  pressure  resulting  from  stimulation  of  the  central  end  of  the 
sciatic  was  accompanied  by  a  rise  of  pressure  in  the  femoral  vein  of 
the  other  leg.  In  the  exceptional  cases  where  no  rise  was  obtained, 
there  was  either  no  change  in  venous  pressure  or  only  a  slight  fall. 
This  result  can  not,  under  the  conditions  of  the  experiment,  be  a 
passive  phenomenon,  and  I  am  convinced  from  a  number  of  obser- 
vations, that  the  respiratory  reflexes  can  not  be  regarded  as  the  cause 
of  it.  It  seems  to  be  due  to  an  active  dilatation  of  the  vessels  of 
the  limb.^ 

The  effect  on  the  portal  pressure  was  not  so  constant,  but  the  result 

1  Brunton  and  Tunnicliff  e  (loc.  cit.)  have  shown  that  when  a  considerable  mass  of 
muscle  is  kneaded  there  occurs  along  with  the  fall  of  arterial  pressure  a  great  increase  in 
the  outflow  from  the  veins  of  the  muscles  kneaded. 

27—2 


400  R-   HUNT. 

was  usually  a  fall.  Whether  this  was  due  to  active  changes  or  was 
merely  passive  seems  at  present  impossible  to  determine.  Figure  4 
shows  these  results  in  one  experiment. 


•'vv^vAvvvv^..vvv.'l,/'v^H^'^^'*'^•'^^ 


FEMORAL 


I    I    I    I    I    i    I    t    I    t    I    I    I    I    I    i^l    I    I    t    ^    I    I    I    I    I    I    t    I    t    t    I    t    t    II    I    I    I   I    ^ 


—\. 


Fig.  4.  Dog.  Ether.  Vagi  intact.  Fall  of  pressure  in  carotid  and 
portal  vein,  and  rise  in  femoral  vein  on  stimulation  of  sciatic  at  10°.  All 
the  curve.s  have  the  same  base  line ;  the  curves  of  venous  pressure  being 
drawn  to  indicate  the  pressure  in  mm.  NaoCOg,  the  curve  of  arterial  pressure 
in  mm.  Hg.  The  changes  of  pressure  in  the  curves  must  be  multiplied  by  2 
to  obtain  the  absolute  changes.     Tracing  from  right  to  left. 

All  three  curves  are  drawn  to  a  common  base  line.  The  arterial 
pressure  is  expressed  in  mm.  Hg.;  the  venous  in  mm.  Na^COj  solution. 
To  show  the  absolute  changes  in  pressure  the  distances  of  the  cupve 
must  be  multiplied  by  two.  Both  the  fall  of  arterial  and  the  rise  of 
venous  (femoral)  pressure  were  slight  in  this  experiment.  In  some  they 
were  20  and  27  mm.  Hg.  and  20  and  30  mm.  Na^COj  respectively,  the 
venous  pressure  being  in  such  cases  almost  doubled.  Similar  effects 
upon  venous  pressure  were  observed  when  a  fall  of  arterial  pressure 
resulted  from  cooling  and  stimulating  the  ulnar  or  median. 

It  is  interesting  to  compare  with  these  results  the  effect  on  arterial 
and  venous  pressure  of  stimulating  the  central  end  of  the  vagus.  This, 
as  is  well  known,  often  causes  a  fall  of  arterial  pressure  which  has  been 
attributed  to  an  inhibition  of  the  vaso-constrictor  centre  and  a  con- 
sequent dilatation  of  the  arteries,  especially  those  in  the  visceral  area. 
If  this  supposition  is  correct,  we  should  expect  to  find  little  or  no 
change  in  the  pressure  in  the  femoral  vein,  while  the  dilatation  in  the 
splanchnic  area  might  cause  a  rise  of  portal  pressure.  This  is,  in  fact, 
what  was  found  in  a  number  of  experiments  (see  Figs.  5  and  6). 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        401 


^V^'^'^Vv^HvvVvv.vvv^^ 


CAROTID 


4.t«,tilltttllll«lli«lllfllltllitltlll.»i«...)f......,,...^,,.^^,f 


1  L. 

Fig.  5.  Curves  similar  to  above  to  show  changes  in  portal  and  carotid 
pressure  from  stimulation  of  central  end  of  vagus.  Dog.  Morphia  and 
Curare.     Tracing  from  right  to  left. 


FEMORAL 


i  I  I  I  I  I  I  I  I  I  I  i  I  1  I  I  I  i  I  i  «  I  I  I  f  i  i  I  I  i  I  I  I  1  i  i  I  I  I  i  i 


I 


Fig.  6.  Curves  showing  changes  in  pressure  in  femoral  vein  and  carotid 
from  stimulation  of  central  end  of  vagus.  Dog.  Morphia  and  Curare.  The 
arterial  pressure  returned  from  the  fall  slowly.      Tracing  from  right  to  left. 

The  rise  of  portal  pressure  is  often  not  very  marked,  but  the  fact  that 
a  large  fall  of  arterial  pressure  may  occur  without  any  change  in  that  of 
the  femoral  vein,  indicates  that  the  dilatation  in  such  cases  is  largely 
elsewhere  than  in  the  limbs.  It  is  probably  of  visceral  origin.  The 
fall  of  arterial  pressure  is  sometimes  accompanied  by  a  fall  in  that  of 
the  femoral  vein.     This  is  probably  a  passive  effect. 

Two  other  experiments  indicate  that  the  dilatation  occurs  elsewhere 
than  in  the  splanchnic  area.  The  first  of  these  was  made  upon  a  dog. 
The  coeliac  axis,  the  renal  and  the  superior  mesenteric  arteries  and  the 
portal  vein  were  ligated ;  cophng  and  stimulating  the  sciatic  continued 
to  cause  a  fall  of  pressure.  In  one  case  the  fall  amounted  to  28  mm. 
The  aorta  was  now  tied  above  the  inferior  mesenteric  and  the  radial 
stimulated.     A  fall  of  pressure  was  still  obtained.    In  the  other  experi- 


402  R.   HUNT. 

ineut  the  out-flow  from  a  branch  of  the  femoral  vein  was  measured ;  the 
sciatic  of  the  opposite  side  was  stimulated.  In  each  case  the  aortic 
pressure  fell  on  stimulation  while  the  out-flow  from  the  vein  was 
increased.  Sometimes  the  increase  was  607o-  There  seem  to  have 
been  no  changes  in  respiiation  as  a  result  of  stimulation. 

Part  IV.    General  consideration  of  results. 

The  entire  subject  of  reflex  vaso-motor  actions  is  so  complex  and 
so  little  understood,  that  the  explanation  of  the  above  experiments  is 
attended  with  many  difficulties. 

In  considering  the  results  of  these  experiments  it  will  be  best  to 
take  up,  in  the  first  place,  the  evidence  they  afford  for  the  existence  in 
ordinary  sensory  nerves  of  two  sets  of  afferent  fibres  to  the  vaso-motor 
centre,  a  set  of  pressor  fibres  which  cause  a  reflex  rise  of  blood-pressure, 
and  a  set  of  depressor  fibres,  stimulation  of  which  leads  to  a  fall  of 
pressure.  In  the  second  place,  the  question  as  to  the  manner  in  which 
the  dilatation  leading  to  a  fall  of  pressure  is  brought  about — whether, 
for  example,  it  is  due  to  a  stimulation  of  vaso-dilator  fibres  or  to  an 
inhibition  of  constrictors — may  be  considered  as  far  as  the  facts  will 
permit. 

Is  the  reflex  fall  of  blood-pressure  due  to  the  action  of  "depressor 
fibres,"  or  does  it  depend  upon  the  condition  of  the  vaso-motor  centre  ? 

As  stated  above,  the  second  of  these  hypotheses  seems  to  have 
gained  most  credit  with  physiologists,  and  there  are  many  facts  whiph 
indicate  that  the  condition  of  the  centres  does  modify  profoundly  the 
result  of  stimulating  afferent  nerves.  Thus  vaso-motor  reflexes  obtained 
from  animals  in  which  the  cerebral  hemispheres  are  intact  differ  from 
those  observed  when  these  parts  are  removed  ^ — a  fact  which  is  probably 
explained  by  the  condition  of  "  shock  "  of  the  centres  in  the  medulla, 
resulting  from  the  operation.  In  the  experiments  recorded  in  this 
paper,  however,  where  the  nerve  stimulated  was  subjected  to  the  action 
of  cold,  or  stimulation  was  applied  to  a  regenerating  nerve,  no  change 
can  be  supposed  to  have  occurred  in  the  centre ;  the  action  in  these 
cases  must  have  been  upon  the  nerve  fibres  themselves.  There  are 
other  cases,  notably  those  in  which  certain  anaesthetics  or  other  drugs 
are  used,  where  it  is  difficult  to  determine  whether  the  centres  alone 
are  acted  upon  or  whether  the  nerve  fibres  are  involved.  It  will  be 
best  to  consider  these  various  cases  separately. 
1  See  Knoll.     Op.  cit.  p.  456. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        403 

1.  Methods  hy  which  a  reflex  fall  of  blood-pressure  can  he  obtained 
without  any  change  being  produced  in  the  vaso-motor  centre. 

The  chief  methods  are  as  follows : 

(1)  Stimulation  of  afferent  nerves  when  cooled,  (2)  stimulation  of 
regenerating  nerves,  (3)  stimulation  of  nerves  which  have  been  sub- 
jected to  rough  treatment  or  exposure,  (4)  employment  of  weak  stimu- 
lation, (5)  the  mechanical  stimulation  of  muscles.  It  is  apparent  at 
once  that  in  none  of  these  cases  can  the  reflex  fall  of  pressure  be 
attributed  to  a  change  in  the  condition  of  the  vaso-motor  centre ;  the 
only  part  of  the  reflex  arc  altered  by  these  agencies  is  the  afferent 
nerves.  As  it  is  difficult  to  suppose  that  the  same  nerve  fibres  can  at 
one  time  carry  impulses  having  one  effect,  and  at  another  impulses 
having  exactly  the  opposite  effect  (the  condition  of  the  centre  remain- 
ing the  same),  the  simplest  explanation  of  the  fall  of  pressure  in  the 
above  cases  is  that  there  are  two  sets  of  afferent  fibres ;  we  may 
suppose  one  set  to  make  such  connections  with  the  centres  that  im- 
pulses passing  up  it  cause  a  fall  of  blood-pressure,  while  the  other 
carries  impulses  producing  a  rise. 

That  there  are  fibres  which  affect  the  vaso-motor  centre  in  such  a 
way  as  to  cause  a  fall  of  blood-pressure,  no  one  doubts,  but  they  are 
usually  supposed  to  come  entirely  from  the  heart  and  to  run  in  the 
special  "  depressor  nerve,'"'  or,  if  this  is  wanting,  in  the  trunk  of  the 
vagus;  in  the  latter  case  they  are  mixed  with  ordinary  "pressor" 
fibres.  If  the  existence  of  ''  depressor  "  fibres  is  admitted  in  this  case, 
it  seems  much  simpler  to  explain  the  depressor  effects  from  other 
afferent  nerves  in  a  similar  manner. 

Moreover  there  is  a  more  or  less  regular  gradation  in  the  effects 
upon  the  vaso-motor  centre  produced  by  certain  nerves.  At  one  end 
we  have  the  depressor  of  the  heart  which,  according  to  most  observers, 
always  causes  a  fall  of  blood-pressure ;  next  the  vagus  of  the  dog  and 
cat,  which  causes  sometimes  a  fall,  sometimes  a  rise  of  pressure,  and 
the  glossopharyngeal,  which  usually  gives  a  fall ;  then  come  such  mixed 
nerves  as  the  sciatic,  anterior  crural,  ulnar,  median,  the  intercostals, 
and  the  dog's  and  rabbit's  saphenous,  from  which  depressor  effects  are 
obtained  usually  by  special  means ;  and  finally  we  have  the  cat's 
saphenous  and  the  splanchnic,  which  very  rarely  under  any  circum- 
stances, give  a  reflex  fall  of  pressure  on  stimulation.  It  seems  almost 
necessary  to  suppose  that  the  fibres  of  these  various  nerves  make 
different  connections  with  the  vaso-motor  centre  or  centres ;  if  this  is 
admitted,  then  we  must  admit  that  the  fibres  are    different   in   the 


404  /?.    HUNT. 

sense  in  which  we  are  using  the  word,  that  is,  they  constitute  two 
diflferent  physiological  varieties  of  afferent  fibres. 

The  only  alternative  hypothesis  which  presents  itself  would  be 
somewhat  as  follows.  We  might  suppose  one  nerve  fibre  to  be  con- 
nected with  both  a  dilator  and  a  constrictor  centre  ;  and  perhaps  we 
might  further  imagine  that  a  weak  stimulus  could  reach  or  excite  one 
centre  more  readily  than  the  other,  owing  to  a  difference  in  irritability. 
In  such  a  case  the  result  of  stimulating  the  afferent  fibre  would  be 
largely  determined  by  such  factors  as  the  strength  and  nature  of  the 
stimulus  and  the  condition  of  the  centres.  But  such  a  hypothesis 
would  not  explain  why,  when  all  the  other  conditions  are  the  same,  a 
depressor  effect  is  obtained  so  much  more  readily  from  one  nerve,  e.g. 
the  sciatic,  than  from  another,  e.g.  the  splanchnic.  Here  again  we 
should  have  to  suppose  a  difference  in  the  central  connections,  the 
fibres  of  one  nerve,  for  example,  making  closer  connections  with  one 
centre  than  do  those  from  the  other  nerve.  And  the  same  argument 
would  apply  with  equal  force  to  the  difference  between  the  effects  of  a 
purely  cutaneous  and  a  purely  muscular  stimulation,  the  former  pro- 
ducing a  rise,  the  latter  a  fall  of  blood-pressure. 

From  these  considerations  it  seems  impossible  to  avoid  the  conclu- 
sion that  the  afferent  nerve  fibres  which  cau.se  a  reflex  fall  of  blood- 
pressure  are  anatomically  distinct  from  those  which  cause  a  rise  of 
pressure. 

So  far  nothing  has  been  said  as  to  the  exact  manner  in  which  the 
separation  of  pressor  and  depressor  effects  are  produced  in  the  cases 
where  the  nerve  stimulated  has  been  subjected  to  cold  or  exposure,  or  is 
regenerating.  Granting  that  there  are  two  sets  of  afferent  fibres  making 
different  connections  with  the  vaso-motor  centres,  we  may  suppose  that 
a  fall  of  pressure  under  the  above  circumstances  is  produced  in  one  of 
the  following  ways. 

In  the  first  place,  we  might  suppose  that  the  impulses  started  in 
both  sets  of  nerve  fibres  by  stimulation  are  merely  weakened  by  the 
above  influences ;  and  if  it  is  further  supposed  that  the  dilator  centre  is 
more  irritable  than  the  constrictor  centre,  then  a  point  might  be  reached 
at  which  the  former  only  was  able  to  respond  to  the  weakened  stimulus. 
It  is  well  known  that  different  medullary  centres  do  differ  in  their 
irritability ;  the  respiratory  centre,  for  example,  responds  to  stimuli  too 
weak  to  aflfect  the  vaso-motor  centre  and,  as  has  been  described  above,  a 
weak  stimulus  applied  to  a  nerve  often  causes  a  fall  of  blood-pressure, 
while  a  stronger  causes  a  rise. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.        405 

But  there  are  several  facts  which  indicate  that  the  weakening  of  the 
impulses  can  play  but  a  subordinate  part  in  the  cases  under  discussion. 
For  example,  a  much  greater  fall  of  pressure  can  be  obtained  when  the 
nerve  is  cooled  and  stimulated,  than  can  be  obtained  by  the  use  of  a 
weak  stimulus  alone.  Also  stimulation  of  a  regenerating  nerve  may 
produce,  with  the  fall  of  blood-pressure,  marked  respiratory  and  cardiac 
reflexes,  which  indicate  that  the  stimulus  could  not  have  been  very 
weak. 

We  are  therefore  led  to  the  alternative  hypothesis  as  to  the  mode  of 
action  of  the  above-mentioned  agencies  in  separating  the  depressor  and 
pressor  effect,  namely,  that  when  the  nerve  is  cooled  or  is  subjected  to 
exposure,  the  pressor  fibres  lose  their  power  of  conducting  impulses  more 
easily  than  do  the  depressor,  and  that  in  the  case  of  a  regenerating  nerve 
the  latter  class  of  fibres  grow  down  or  become  functional  earlier  than  do 
the  former. 

This  explanation  of  the  action  of  cold  is  the  one  proposed  by  Howell, 
who  gives  also  several  similar  instances  of  the  differential  action  of  cold 
upon  different  nerve  fibres  combined  in  a  common  trunk.  As  regards 
regenerating  nerves,  there  are  already  a  number  of  facts  which  indicate 
that  the  fibres  in  a  nerve  trunk  regenerate,  as  well  as  degenerate,  at 
different  rates.  Thus,  as  was  mentioned  above,  Howell  finds  that  when 
the  sciatic  is  cut  and  the  ends  sutured  together,  the  vaso-dilators  re- 
generate earlier  than  do  the  vaso-constrictors;  Ostroumoff  ^  showed  that 
the  vaso-constrictors  degenerate  more  rapidly  than  do  the  vaso-dilators, 
and  Mott  ^  has  recently  stated  that  there  is  evidence  to  show  that  the 
afferent  fibres  in  the  spinal  cord  degenerate  at  different  rates  after 
section  of  a  posterior  root. 

2.  Action  of  ancesthetics  and  of  curare.  It  is  well  known  that  when 
some  anaesthetics,  notably  chloral  and  chloroform,  are  employed,  the 
usual  rise  of  pressure  is  often  replaced  by  a  fall,  while  when  curare  is 
given,  a  reflex  rise  is  easily  and  constantly  obtained. 

The  exact  nature  of  the  action  of  these  drugs  has  not  been  deter- 
mined, but  the  usual  belief  is  that  the  drugs  affect  the  nerve  centres. 
This  explanation  seems  very  probable,  when  it  is  remembered  that 
nerve  centres  are  in  general  more  sensitive  to  the  action  of  drugs  than 
nerve  fibres;  and  that  some  of  these  anesthetics,  for  example  chloroform, 
cause  a  fall  of  pressure,  due  most  probably  to  a  partial  paralysis  of  the 
vaso-constrictor  centre.     Still  the  possibility  of  a  "differential  action," 

1  Ostroumoff.    PJliigefs  Archiv,  xn.  228.    1876, 

2  Mott.     Brain,  Part  i,  1892,  p.  2. 


406  R.   HUNT. 

to  some  extent  at  least,  upon  the  afferent  fibres,  is  not  disproved.  A 
few  experiments  made  by  applying  some  of  these  drugs  (chloral,  curare, 
and  morphia)  directly  to  the  nerve  trunk,  or  by  injecting  them  into  it 
with  a  hypodermic  syringe,  gave  negative  results  as  far  as  any  change  in 
conductivity  or  irrita,bility  was  concerned.  But  such  experiments  show 
little,  for  the  conditions  were  very  different  from  those  which  exist  when 
the  drug  is  carried  by  the  blood  and  the  entire  length  of  the  nerve  is 
exposed  to  its  action.  Ether,  applied  to  the  nerve,  blocked  the  afferent 
impulses,  but  no  separation  of  pressor  and  depressor  effects  was  ob- 
served \ 

In  this  connection  may  be  mentioned  again  the  "after-effects"  on 
the  blood-pressure  of  stimulating  afferent  nerves,  especially  in  animals 
poisoned  by  curare  or  anaesthetised  by  brain  compression.  As  was 
described  above,  the  rise  of  pressure  so  obtained  is  often  followed  by  a 
marked  fall.  On  the  hypothesis  that  in  afferent  nerves  there  are  two 
sets  of  fibres  leading  to  the  vaso-motor  centre,  we  may  suppose  that 
both  are  excited  simultaneously  when  the  nerve  is  stimulated,  but  that 
the  depressor  fibres  have  a  long  "after-effect";  hence  the  fall  of  pressure 
after  the  stimulation  ceases.  This  supposition  would  be  similar  to  the 
one  by  which  Roy  and  Adami-  explain  the  vagus  effects  upon  the 
heai't  which  occur  after  the  cessation  of  the  stimulation  of  afferent 
nerves  (the  heart  being  accelerated  during  stimulation),  and  to 
Meltzer's'  theory  of  the  after-effects  on  the  respiratory  centre  from 
stimulating  the  central  end  of  the  vagus,  according  to  which  the  in- 
hibitory fibres  exert  their  influence  during,  and  the  inspiratory  after,, 
stimulation.  This  after-effect  on  the  blood-pressure  often  occurs  only  in 
the  eai-ly  part  of  experiments  on  curarised  animals.  When  the  fact  is 
remembered  that  curare  seems  to  diminish  the  irritability  of  the  depres- 
sor mechanism  in  general  (or  to  increase  that  of  the  pressor  mechanism, 
so  that  when  both  are  thi'own  into  action  the  latter  predominates),  the 
disappearance  of  the  after-effect  may  be  taken  to  indicate  that  this 

1  That  curare  has  a  marked  effect  upon  the  terminations  of  sensory  nerves  seems 
scarcely  open  to  doubt.  Heidenhain  and  Griitzner  (PjViyer's  Archiv,  xvi.  54—56, 
1877)  showed  that  often  a  slight  stimulation  of  the  hair  of  a  curarised  rabbit  produced  a 
much  greater  rise  of  blood-pressure  than  a  strong  electrical  stimulus  applied  directly  to 
the  nerve  and,  as  was  shown  above,  a  greater  fall  of  pressure  could  be  obtained  by  kneading 
the  muscles  of  a  curarised  animal  than  from  one  simply  anaesthetised;  in  fact  a  fall  of 
pressure  can  usually  be  obtained  in  this  manner  from  a  curarised  animal,  while  cooUng  and 
stimulating  the  nerve  are  usually  ineffective. 

-  Roy  and  Adami.     Phil.  Trans,  vol.  183 B,  259.   1892. 

'  Meltzer.     New  York  Medical  Journal,  51,  p.  59.    1890. 


AFFERENT  NERVES   ON  BLOOD-PRESSURE.  407 

mechanism  is  rapidly  paralyzed  or  easily  exhausted  when  this  drug  is 
employed.  Though  it  is  not  definitely  proved,  the  simplest  supposition 
is  that  the  drug  acts  directly  upon  the  centres ;  thus  the  vaso-dilator 
centre  may  be  supposed  to  be  affected  before  the  constrictor  centre. 
That  the  constrictor  centre  may  also  be  affected  is  shown  by  the  absence 
of  a  reflex  rise  of  pressure  after  a  large  dose  of  curare. 

What  appears  to  be  the  opposite  effect,  viz.,  a  rapid  paralysis  or 
exhaustion  of  the  pressor  mechanism,  is  often  observed  in  experiments 
on  etherised  animals,  especially  it  seems  upon  rabbits.  In  such  experi- 
ments the  effect  of  the  first  two  or  three  stimulations  may  be  a  rise  of 
pressure,  after  which  only  a  fall  can  be  obtained.  The  chief  factor  in 
diminishing  the  irritability  of  the  pressor  mechanism  is  doubtless  the 
direct  action  of  the  ether  upon  the  constrictor  centre,  though  the 
possibility  of  some  action  upon  the  afferent  nerve  fibres  can  not  be 
excluded.  That  the  latter  supposition  is  possible  seems  to  be  shown  by 
the  fact  that,  after  one  sciatic,  for  example,  has  been  stimulated  till  a 
reflex  fall  of  pressure  is  obtained  (a  rise  of  pressure  having  followed  the 
stimulations  at  first),  stimulation  of  the  nerve  on  the  opposite  side  will 
cause,  for  a  short  time,  a  rise  of  pressure.  This  may  be  taken  to  indicate 
a  weakening  of  the  power  to  conduct  impulses  on  the  part  of  the  pressor 
fibres  of  the  nerve,  or,  on  the  other  hand,  to  show  that  when  the  con- 
strictor centre  is  partially  paralyzed  by  the  ether,  some  of  its  parts  are 
still  able  to  respond,  for  a  time,  to  impulses  coming  up  the  pressor  fibres 
after  other  parts  have  been  completely  exhausted  by  stimulation.  The 
question  which  of  these  suppositions  is  correct,  as  well  as  the  entire 
problem  of  a  differential  action  of  drugs  upon  the  afferent  fibres,  must 
be  left,  for  the  present,  undecided. 

The  nature  of  the  reflex  vaso-dUatation  resulting  from  stimulation  of 
the  setisory  nerves.  The  data  for  determining  the  manner  in  which  reflex 
vaso-dilatation  is  brought  about,  whether  by  an  inhibition  of  constrictors 
or  by  a  stimulation  of  dilators,  or  by  both  agencies,  are  too  few  to  make 
speculation  of  much  value.  But  it  at  least  seems  very  probable,  that 
the  mechanism  concerned  when  the  fall  of  pressure  results  from  stimula- 
tion of  ordinary  sensory  nerves,  is  different  from  that  called  into  play  in 
the  dilatation  resulting  from  stimulation  of  the  depressor  or  of  the  vagus. 
In  the  former  case  the  dilatation  occurs  to  a  much  greater  extent  in  the 
muscular  system,  and  to  a  less  extent  in  the  splanchnic  area,  than  is  the 
case  with  the  latter  nerves.  Another  point  of  difference  is  the  effect  of 
curare  in  the  two  cases  :  while  this  drug  usually  makes  it  difiicult  or 
impossible  to  obtain  a  fall  of  pressure  from  stimulating  the  sciatic  and 


408  R.   HUNT. 

similar  nerves,  it  seems  to  have  little  or  no  effect  upon  the  reflex  fall 
from  stimulation  of  the  depressor  or  vagus.  Both  these  points  of  differ- 
ence are  readily  explained,  if  we  assume  that  the  dilatation  following 
stimulation  of  the  depressor  or  the  depressor  fibres  in  the  vagus  is  due 
to  an  inhibition  of  the  constrictor  centre,  while  that  following  stimulation 
of  the  sciatic  and  similar  nerves  is  due  to  a  stimulation  of  the  dilator 
centre,  since  in  a  fall  of  pressure  produced  by  the  latter  method  we 
should  expect  the  dilatation  to  occur  chiefly  in  the  muscular  system  where 
the  dilator  fibres  predominate,  while  if  the  fall  of  pressure  resulted  from 
an  inhibition  of  constrictor  fibres  we  should  expect  the  dilatation  to 
occur  mainly  in  the  great  splanchnic  area  where  the  constrictor  fibres 
predominate.  So  also  the  action  of  curare  in  the  two  cases  is  explained 
on  the  above  assumption,  since  it  is  well  known  that  this  drug  in  the 
usual  doses  increases  the  irritability  of  the  vaso-constrictor  centre,  and 
we  should  therefore  expect  that  it  would  not  prevent  the  occurrence  of 
a  dilatation  due  to  an  inhibition  of  the  constrictor  fibres  as  we  assume 
to  be  the  case  with  the  depressor  nerve ;  whereas  curare,  according  to 
GaskelP,  Eckhard*^  and  v.  Frey^  diminishes  the  irritability  of  the 
dilator  fibres  and  should  therefore  tend  to  destroy  or  weaken  a  dilatation 
due  to  a  reflex  stimulation  of  the  dilator  fibres  as  we  assume  to  be  the 
case  in  the  fall  of  pressure  caused  by  stimulation  of  the  sciatic,  etc. 

The  different  effects  obtained  from  stimulation  of  various  nerves  in 
animals  in  which  the  blood-pressure  has  fallen  as  a  result  of  the  admini- 
stration of  ether  or  chloroform,  or  after  exhausting  operations,  are  also 
more  easily  explained  by  this  view.  Some  of  my  records  show  that  - 
while  the  blood-pressure  was  high,  stimulation  of  the  vagus  caused  a 
marked  fall  of  pressure,  that  of  the  sciatic  a  rise ;  when,  however,  the 
pressure  had  fallen  after  the  administration  of  ether  or  the  opening  of 
the  abdominal  cavity,  stimulation  of  the  vagus  no  longer  caused  a  fall  of 
pressure,  while  there  was  often  a  marked  fall  from  stimulation  of  the 
sciatic.  If  we  suppose,  therefore,  that  the  fall  of  pressure  from  stimula- 
tion of  the  vagus  is  due  to  an  inhibition  of  the  constrictor  centre  and 
that  after  etherisation,  exhausting  operations  etc.,  this  effect  disappears 
in  consequence  of  a  partial  paralysis  of  the  vaso-constrictor  centre,  the 
continuance,  and  indeed  augmentation,  of  the  depressor  effect  upon 
stimulation  of  the  sciatic  under  these  conditions  can  scarcely  be  referred 
to  an  inhibition  of  the  constrictor  centre,  since  this  is  apparently  in  a 

1  Gaskell.     This  <7ouni«Z,  i.  273.   1878— Q. 

*  Eckhard.     Beitrage  z.  Anatomie  u.  Physiologic,  vii.  75.    1876. 

*  V.  Frey.     Ludwig's  Arbeiten,  ii.  89.    1876. 


AFFERENT  NERVES  ON  BLOOD-PRESSURE.        409 

condition  of  depressed  irritability.  Hence  the  alternative  view,  that  the 
fall  of  pressure  is  due  to  a  reflex  stimulation  of  the  dilator  fibres,  seems 
more  probable  in  these  cases  also\ 

If  we  adopt  this  view  it  would  be  better  to  use  the  word  '  depressor ' 
in  its  original  sense,  i.e.  to  denote  all  afferent  nerve-fibres  producing 
dilatation  by  inhibiting  the  constrictor  centre ;  and  to  use  some  other 
term,  such  as  "reflex  vaso-dilator "  (which  was  employed  by  Howell), 
in  those  cases  where  the  fall  of  pressure  is  produced  by  the  stimulation 
of  dilator  fibres. 

Summary  of  results. 

(1)  A  reflex  fall  of  blood-pressure  was  obtained  upon  stimulation  of 
the  sciatic  and  other  mixed  nerves  by  the  following  methods. 

(a)  Stimulation  of  nerves  which  had  been  subjected  to  the  action 
of  cold. 

(b)  Stimulation  of  regenerating  nerves. 

(c)  The  use  of  weak  stimulation. 

(d)  The  mechanical  stimulation  of  nerves  ending  in  muscles. 

(2)  In  none  of  the  above  cases  can  the  result  be  attributed  to  an 
abnormal  condition  of  the  vaso-motor  centre. 

(3)  There  is  very  strong  evidence  for  the  view  that  there  are 
"depressor"  or  "reflex  vaso-dilator"  fibres  in  the  sciatic  and  similar 
nerves. 

(4)  When  a  mixed  nerve  is  cooled  or  is  subjected  to  exposure,  these 
fibres  retain  their  power  of  conductivity  longer  than  do  the  "pressor" 
fibres ;  when  the  nerve  is  cut  and  sutured,  they  regenerate  earlier  than 
do  the  latter. 

(5)  Anaesthetics  and  curare  have  a  marked  effect  upon  the  ease 
with  which  a  reflex  fall  of  pressure  is  obtained  ;  ether,  chloroform  and 
chloral  are  favourable,  curare  unfavourable,  to  its  occurrence. 

(6)  The  action  of  these  drugs  is  probably  largely  upon  the  centres ; 
the  above-mentioned  ansesthetics  probably  paralyzing  the  constrictor, 
curare  the  dilator  centre. 

(7)  The  fall  of  pressure  from  stimulation  of  the  sciatic  and  of  simi- 
lar nerves  is  of  a  different  nature  from  that  resulting  from  stimulation  of 

1  Bayliss  (This  Journal,  xiv.  322.  1893)  supposes  that  the  fall  of  pressure  following 
stimulation  of  the  depressor  nerve  or  the  depressor  fibres  in  the  vagus  is  due  mainly  to  a 
stimulation  of  the  dilator  centre,  while  the  similar  fall  from  stimulation  of  the  anterior 
crural  is  due  mainly  to  an  inhibition  of  the  constrictor  centre,  but  it  is  difficult  to  discover 
in  his  paper  from  what  evidence  he  draws  this  conclusion. 


410  R   HUNT. 

the  depressor  or  vagus  ;  in  the  former  case  the  dilatation  occurs  largely 
in  the  limbs  and  curare  is  distinctly  unfavourable  to  its  occurrence ;  in 
the  latter  case  the  dilatation  occurs  to  a  much  less  extent  in  the  limbs 
and  curare  does  not  seem  to  materially  affect  the  ease  with  which  it  is 
obtained. 

(8)  The  fall  of  pressure  following  upon  stimulation  of  mixed  nerves 
is  probably  due  to  a  reflex  stimulation  of  dilator  fibres. 

(9)  It  seems  desirable  to  apply  the  name  "  depressor"  only  to  those 
fibres  which  inhibit  the  vaso-constrictor  centre  and  to  use  "  reflex  vaso- 
dilator" for  the  fibres  exciting  the  vaso-dilator  centre. 

In  conclusion  I  desire  to  express  my  sincere  thanks  to  Prof  Howell, 
at  whose  suggestion  this  work  was  undertaken  and  to  whom  I  am  in- 
debted for  much  aid  and  many  valuable  suggestions. 


VITA. 

The  author  of  this  thesis  was  born  at  Martinsville,  Ohio,  in  April, 
1870.  He  was  prepared  for  college  in  the  public  schools  of  Ohio  and 
in  the  preparatory  department  of  Wilmington  College.  After  spend- 
ing a  year  in  the  Ohio  University,  he  entered  the  collegiate  depart- 
ment of  the  Johns  Hopkins  University  in  1888.  He  received  the 
degree  of  A.  B.  in  June,  1891.  The  year  1891-92  was  spent  in  study, 
partly  in  the  Johns  Hopkins  University  and  partly  in  the  University 
at  Bonn.  Returning  to  the  Johns  Hopkins,  he  acted  as  Assistant  in 
Histology  and  Physiology  1892-93,  and  in  Physiology  1893-94.  In 
June,  1894,  he  was  appointed  Fellow  in  Physiology  and  was  reap- 
pointed in  June,  1895. 


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